Abstract Objective To compare patient reports of intraoperative pain and postoperative side effects by different anesthesia strategies for cataract surgery. Design Prospective cohort study. Participants Men and women 50 years of age and older undergoing 19,250 cataract surgeries at nine centers in the United States and Canada from June 1995 through June 1997. Intervention Topical anesthesia or anesthesia with injection, with or without sedatives, opioid analgesia, hypnotics, and diphenhydramine (Benadryl). Main outcome measures Patient ratings of intraoperative pain, satisfaction with pain management, and early postoperative side effects (drowsiness, nausea, vomiting, or a combination thereof). Results Twenty-six percent of surgeries were performed using topical anesthesia alone, and the remainder were performed with peribulbar, retrobulbar, or facial nerve block, or a combination thereof. Local anesthesia by injection with sedatives and diphenhydramine resulted in the lowest reporting of any intraoperative pain (1.3%), with postoperative drowsiness (9.6%) and nausea, vomiting, or both (1.5%) comparable with those administered topical anesthesia alone. Among those receiving topical anesthesia, use of sedatives and opioids reduced reports of any pain during surgery by 56% (95% confidence interval [CI], 34%, 70%), but increased nausea and vomiting (odds ratio, 2.27; 95% CI, 1.26, 4.09) compared with those administered topical anesthesia alone, after adjusting for age, gender, race, American Society of Anesthesiologists risk class, self-reported health status, and duration of surgery. Among those receiving local injections, use of opioids reduced reports of any pain among those receiving sedatives by 37% (95% CI, 15%, 54%), but did not increase postoperative side effects. The use of diphenhydramine among those receiving sedatives decreased reports of any pain by 59% (95% CI, 33%, 75%) and also reduced drowsiness and nausea and vomiting by 57% (95% CI, 48%, 65%) and by 60% (95% CI, 36%, 75%), respectively. Use of hypnotics with sedatives was associated with increased reports of any pain during surgery and increased nausea and vomiting after surgery. Conclusions Patient reports of any pain during cataract surgery (5%) and postoperative side effects (16% drowsiness and 4% nausea and vomiting) were low, but varied by anesthesia strategy. Patient perceptions of pain and side effects can be helpful in guiding the appropriate choice of anesthesia strategy.